Blood-brain barrier serves as a CNS entry route for SARS-CoV-2
2022
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Hamburg, Germany(1)
University Medical Center Hamburg-Eppendorf, Hamburg, Germany(2)
University Medical Center Hamburg-Eppendorf, Hamburg, Germany(2)
Although SARS-CoV-2 has been detected in the brain tissue of patients, its entry pathways and resulting consequences are not well understood. In this study, the researchers demonstrate a distinct upregulation of interferon signalling pathways in the neurovascular unit in lethal COVID-19. Examined the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) to SARS-CoV-2 infection and found that BCECs were infected and recapitulated the transcriptional changes detected in vivo. While BCECs were unaffected in their paracellular tightness, SARS-CoV-2 was found in the basolateral compartment in transwell assays after apical infection, suggesting active replication and transcellular transport of the virus across the blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. Taken together, the data demonstrate that SARS-CoV-2 enters the brain via the BBB and leads to increased interferon signalling.
The blood-brain barrier is dysregulated in COVID-19 and serves as a CNS entry route for SARS-CoV-2
Ole Pless(1), Susanne Krasemann(2)
Added on: 07-07-2022
[1] https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(21)00650-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213671121006500%3Fshowall%3Dtrue
